The aim of this project is to address whether nebulized heparin:1) increases the number of ventilator*free days during 28*days in burn patients with inhalation trauma2) improves lung injury scores in burn patients with inhalation trauma3) reduces…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Number of ventilator-free days during the first 28 days after inclusion.
Secondary outcome
- clinical outcome parameters such as Lung Injury Score (LIS), ICU
length-of-stay (LOS), 28- and 90-day mortality, incidence of pneumonia (CDC
criteria) and number of bronchoscopies performed to remove foreign particles
and accumulated secretions
- pulmonary coagulation and fibrinolysis as reflected by tissue factor (TF),
activated factor VII (FVIIa) antithrombin (AT), thrombin-antithrombin complexes
(TATc) and activated protein C (APC), plasminogen activator activity (PAA),
tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA) and
plasminogen activator inhibitor 1 (PAI*1), and FDP in BALF
- pulmonary inflammation as reflected by IL*1 beta, IL*6, IL-8, IL-10,
TNF-alpha, VEGF and TGF-beta
- safety of nebulized heparin, as reflected by activated partial thromboplastin
(aPTT) time, prothrombin time (PT) and blood thrombocyte count
Background summary
Inhalation trauma is a major cause of morbidity and mortality in burn patients,
but the underlying pathophysiological mechanisms of inhalation trauma are
poorly understood. Thermal injury and inhaled toxins are thought to destroy the
airway mucosa, subsequently leading to an inflammatory response, vascular
leakage, pulmonary edema and impaired gas exchange. We have previously shown
that the inflammatory response in burn patients with inhalation trauma is
associated with severe pulmonary coagulopathy as compared to non-injured lungs.
Since local administration of heparin has been shown to increase
ventilator-free days in acute lung injury patients, we hypothesize that burn
injury patients with inhalation trauma will have an improved outcome upon
treatment with nebulized heparin.
Study objective
The aim of this project is to address whether nebulized heparin:
1) increases the number of ventilator*free days during 28*days in burn patients
with inhalation trauma
2) improves lung injury scores in burn patients with inhalation trauma
3) reduces pulmonary coagulopathy in burn patients with inhalation trauma
4) impacts pulmonary inflammation in burn patients with inhalation trauma
5) is safe in burn patients with inhalation trauma
Study design
We will perform a multi-center double-blind placebo-controlled trial to
investigate the impact of nebulized heparin on inhalation injury in the lungs
of burn patients. We will include adult burn patients with bronchoscopic
confirmed inhalation trauma.
It will be conducted in three burn centers in the Netherlands (Rode Kruis
Ziekenhuis in Beverwijk, Martini Ziekenhuis in Groningen and Maasstad
Ziekenhuis in Rotterdam) and three burn centers in Belgium (Universitair
Ziekenhuis Leuven, Universitair Ziekenhuis Gent, Ziekenhuis Netwerk Antwerpen
(ZNA) Stuivenberg).
Intervention
Nebulized heparin (25,000 IU) every 4 hrs every 24 hrs for the maximum duration
of 14 days versus placebo (NaCl 0.9%)
Study burden and risks
The burden to the patient is considered to be low. The collection of general
data from hospital charts and (electronic) medical records does not affect the
patients. Blood sampling is combined with routine sampling for standard care of
burn patients. Non-directed bronchial lavage is often used to remove soot from
the bronchial tree and can be considered a safe procedure. At present,
nebulisation of unfractionated heparin is occasionally used in burn patients
with inhalation trauma and has been shown to be safe in a cohort of critically
ill patients. We hypothesize that nebulized heparin accelerates weaning from
mechanical ventilation, which may be a benefit for this treatment arm. This
study may improve standard care for burn patients with inhalation trauma.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- informed consent
- age > 18 years
- need for intubation and mechanical ventilation
- clinical diagnosis of inhalation trauma confirmed by bronchoscopy
Exclusion criteria
- > 36 hours after trauma
- Receiving invasive ventilation > 24 hours
- Expected duration of mechanical ventilation < 24 hours
- Chronic obstructive pulmonary disease GOLD stage III and IV
- Any history of pulmonary hemorrhage in the past 3 months
- Any history of significant bleeding disorder
- Known allergy to heparin, including heparin*induced thrombocytopenia
- Pregnancy or breast feeding
- Unlikely to survive for > 72 hours
- Total body surface area (TBSA) > 60%
- Witnessed or proven aspiration (i.e., confirmed by bronchoscopy)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-003289-42-NL |
| CCMO | NL41399.018.12 |